Continuing research at the Toxicology Center will be directed toward an understanding of how toxic events can be explained and anticipated through knowledge of (1) the regulation of drug metabolism and disposition, (2) developmental pharmacology and toxicology, and (3) basic mechanisms in toxicology. Biochemical, pharmacological and toxicological approaches will be employed. Drugs and toxicants will be examined for their effects on organs and organelles of the liver, adrenal, central nervous system, pancreas and lung. Basic mechanisms that protect or modify toxic events will be investigated in addition to biochemical pathways and basic biological processes susceptible to regulation by drugs and toxicants. Specifically, projects will deal with: the regulation of heme and hemoprotein biosynthesis by drugs, environmental agents and hormones in the developing and adult animal; studies on hepatotoxicity of drugs and envionmental agents; regulation and mechanism of steroidogenesis; studies on the chemistry and mechanism of drug and steroid oxidations; the mechanism of toxicity of glutethimide; the mechanism of pancreatic islet cell toxicity produced by cyproheptadine and its metabolites; the role of hepatic and intestinal morphine conjugating systems; studies on the regulation of oxygen metabolism and toxicity; gonadotropin release; studies on the regulation of oxygen metabolism and toxicity; studies of the effects of drugs, carcinogens and toxicants on membrane biology, the regulation of porphyrias and studies on the role of enterohepatic circulation and biliay excretion of drugs in man. Through an integrated and multidisciplinary approach to research in Toxicology, this Toxicology Center continues to offer a sophisticated environment for the training of future Toxicologists.